tbuckley/cabot-search huggingface dataset:
Abstract 12720: Hypertension in the Dominican Population Living in the United States Enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Compared to Dominicans Living in the Dominican Republic: Understanding the Impact of Risk Factors
Authors: Luisa Alvarez, Ayana K April-Sanders, Un Jung Lee, cesar herrera, Donaldo Collado, Robert Kaplan, Franklyn Gonzalez, Martha L Daviglus, Olga Garcia, Tali Elfassy, Neil Schneiderman, Krista Perreira, Larissa Aviles-Santa, Gregory A Talavera, Leonor Corsino, Carlos Rodriguez
Journal: Circulation (2022)

Background: Hispanics/Latinos of Dominican heritage living in the United States (US) have the highest prevalence of hypertension (HTN) compared with other Hispanic/Latino groups. To better understand cardiovascular health among Dominicans, a primarily immigrant population, it is crucial to examine the unique social contexts that influence their health outcomes. Our objective was to evaluate HTN prevalence and risk factors among individuals of Dominican descent from two social contexts - the US and the Dominican Republic (DR). Methods: HTN among DR Dominicans (DRD) was assessed using data from ENPREFAR-HAS 17, a representative sample of DRD (N=2,016; mean age 40±0.37 years, 60% females, unweighted); while HTN among US Dominicans (USD) was assessed from the HCHS/SOL, a population-based cohort study of Hispanics/Latinos in the US (Dominican subset, N=1,473; mean age 41±.25 years, 50% females, weighted). HTN was defined as blood pressure recording ≥140/90 mm Hg, self-reported HTN, or HTN treatment. Exposures included sociodemographic, lifestyle, and clinical characteristics. Poisson regression analyses were used to estimate associations between study characteristics and the prevalence of HTN (PR = prevalence ratio), adjusting for age and gender. Results: HTN was more prevalent among DRD (31%) than USD (27%). Younger adults (18-39) and females were more likely to have HTN in the DR, while older adults (40-60+) and males had a higher prevalence of HTN in the US. In those with HTN, awareness was common (74% USD, 68% DRD); most were receiving treatment (62% USD, 61% DRD), but overall, HTN control was low (35% USD, 36% DRD). Alcohol use was inversely associated with HTN prevalence for DRD (PR=0.8) with no association among USD. In both settings, diabetes (PR DRD = 1.4; PR USD = 1.4) and increased BMI (PR DRD = 1.8; PR USD = 2.0) were associated with a greater prevalence of HTN. Conversely, physical activity was protective against prevalent HTN among USD (PR=0.80) but associated with increased prevalence of HTN among DRD (PR=1.16); all p&lt;0.05. Conclusions: Variations in social, lifestyle, and clinical characteristics associated with HTN among Dominicans in the US and DR were identified, suggesting that context and cultural issues matters among immigrant populations.
Abstract 11938: Novel Approach for Optimal Assessment of Cardiovascular Risk of Blood Pressure in Asymptomatic Subjects Utilizing Mild Exercise Stress Test Protocol
Authors: Mahfouz El Shahawy, Antonella Sabatini, Lillee Izadi
Journal: Circulation (2022)

Background: BP risk class assessment has been relying on resting BP (rBP) measurements by healthcare providers. Often, this measurement does not correlate with 24-hour ambulatory BP monitoring nor with at-home measurements. Purpose: To assess whether abnormal rise in BP post-mild exercise protocol (PMEP), which resembles most of the activities subjects are under all day, will be more physiologic and informative for risk stratification, beyond the rBP measurements. Methods: We screened 2,924 subjects, ages 20-79, for CVD risk using the Early Cardiovascular Disease Risk Scoring System, also known as the Rasmussen Risk Score, which consists of 10 tests: 7 vascular and 3 cardiac (published previously). The vascular tests include rBP, BP PMEP (2.4 mi/hr and 7% elevation for 3 minutes), small (C2) artery stiffness, and CIMT. Out of the total subjects, 1094 (37%) were asymptomatic and on no medications. These were divided into four BP classes according to the current ACC/AHA guidelines. Results: In the table, normotension with an abnormal rise in BP PMEP has significant cardiovascular structural and functional abnormalities (CVSFA) than those without. Also noted, the higher the BP class, the higher the CVSFA with and without an abnormal rise in BP PMEP. Conclusions: Abnormal rise in BP PMEP in normotensive subjects is associated with significant CVSFA. This may represent a “masked hypertension” cohort. These findings mandate early diagnosis, follow-up, and optimal treatment. Additionally, an abnormal rise in BP PMEP in other classes is more pronounced with stepwise increases in BP class. Hence, we advocate for PMEP for BP classification and treatment. Early detect to protect.
Abstract 10435: Blood Flow Patterns Regulate Efferocytosis in Endothelia Cells
Authors: Shijie Liu, Zufeng Ding
Journal: Circulation (2022)

Introduction: Flowing blood generates a frictional force called shear stress that plays an important role in endothelial dysfunction and atherosclerosis. The disturbed flow (d-flow) pattern causes the preferential localization of atherosclerotic lesions, while regions with steady laminar flow (s-flow) are protected against atherosclerosis. Efferocytosis is a process by which apoptotic tissue is recognized for engulfment by phagocytic cells. Defective efferocytosis promotes advanced atherosclerosis. Hypothesis: We hypothesized that blood flow patterns regulate EC efferocytosis and subsequent endothelial dysfunction and contribute to the development of atherosclerosis. Methods: Primary human aortic ECs (HAECs) were exposed to s-flow and d-flow in a step-flow channel, and the changes of efferocytosis receptors in ECs and endothelial dysfunction were investigated. To investigate whether defective efferocytosis plays a role in endothelial dysfunction, HAECs were transfected with a control plasmid or MerTK CRISPR/Cas9 knockout plasmid. Results and Conclusions: Our results showed that efferocytosis regulators, such as Gas6, Pros1, and MerTK, were upregulated under s-flow conditions while inhibited under d-flow conditions compared to static conditions. Our data also showed that MerTK knockout decreased expression of VE-cadherin and CD31, while increased expression of Snail, Slug, and Twist1 as well as α-SMA, N-cadherin, calponin, and FSP1. Of note, VE-cadherin is a strictly endothelial-specific adhesion molecule located at junctions between ECs. As expected, our data showed that MerTK knockout markedly inhibited VE-cadherin expression, indicating that defective efferocytosis increases endothelial barrier dysfunction. This indicates that MerTK-mediated defective efferocytosis in ECs may play an important role in arterial areas exposed to d-flow where prone to atherosclerosis.
Abstract 11531: Neurodevelopmental Outcomes After Neonatal Tetralogy of Fallot Repair or Palliation: Scope of The Problem and Does Treatment Strategy Matter
Authors: Jeffrey D Zampi, Dawn L Ilardi, Courtney E McCracken, Andrew C Glatz, Asaad Beshish, Bryan H Goldstein, Christopher J Petit, Athar M Qureshi, Caren S Goldberg, Mark A Law, Jeffery J Meadows, Shabana Shahanavaz, Sarosh P Batlivala, Shiraz A Maskatia, Joelle A Pettus, Jennifer C Romano, Kathryn O Stack, Hala Q Khan, Shalin Parekh, George T Nicholson
Journal: Circulation (2022)

Introduction: Neonates with symptomatic tetralogy of Fallot (sTOF) require early intervention with either staged repair (SR; initial palliation with subsequent complete repair) or primary repair (PR). Implications of these neonatal management strategies on late outcomes are not well understood. Thus, we aimed to assess neurodevelopmental (ND) outcomes and identify risk factors for ND concerns. Methods: From 2005-2017, sTOF patients who underwent neonatal intervention across 9 centers were identified. To assess ND, all living patients were sent age-appropriate parent-rating scales of executive function (Behavior Rating Inventory of Executive Function - BRIEF) and psychosocial symptoms (The Behavior Assessment System for Children, 3rd Edition - BASC-3). The results were compared by primary treatment strategy (SR vs. PR) using multivariable models. Patient and clinical factors were compared between those with normal and clinically significant abnormal results (T-score ≥60). Results: Of 572 patients in the initial cohort, surveys were sent to 511 survivors and returned from 144 (28%, 53% male, age 3.2-15.9 years). Up to 37% of respondents had a clinically concerning score on ≥ 1 scales, including 36% with ≥1 abnormal scale present on the BRIEF and 30% with an abnormal scale on the BASC. Across SR and PR strategies, there was no difference in ND outcomes (BRIEF adjusted odds ratio (AOR) 1.55 (0.57, 4.21, p=0.39); BASC AOR 1.13 (0.43, 2.99, p=0.81)). Factors associated with clinically significant executive dysfunction included genetic syndrome (p=0.001), need for invasive ventilatory support (p=0.003) and inotropic support (p=0.01) prior to the index procedure. Only genetic syndrome (p=0.026) was associated with clinically significant psychosocial problems. Conclusions: Late ND abnormalities, specifically executive dysfunction and psychosocial concerns, are common in sTOF patients. While initial treatment strategy does not appear to have impact, intrinsic patient characteristics and pre-procedure measures of clinical severity may predict late ND outcomes and help target increased surveillance for ND complications. Forthcoming analyses will explore existing ND service utilization and parental concerns in the context of these findings.
Abstract 11063: Inequities in Modifiable Cardiovascular Risk Factors Among Women of Childbearing Age With Hypertension Using Life's Simple 7
Authors: Claire Meyerovitz, Philip M Cook, Stephen Juraschek, Didem Ayturk, Sharina PERSON, Tiffany Moore Simas, Stephenie Lemon, Lara Kovell
Journal: Circulation (2022)

Introduction: Cardiovascular disease (CVD) is the leading cause of maternal morbidity and mortality. The American Heart Association’s “Life’s Simple 7” (LS7) highlights seven modifiable factors for promoting cardiovascular health - managing blood pressure (BP), controlling cholesterol, reducing blood sugar, getting active, eating better, maintaining a healthy weight, and not smoking. Hypothesis: We hypothesized there would be racial differences in LS7 factors among women of childbearing age with hypertension (HTN). Methods: Using National Health and Nutrition Examination Surveys from 2001-18, we evaluated LS7 factors among women aged 20-50 years with HTN. HTN was defined as BP ≥140/90 mmHg or anti-hypertensive medication use. LS7 scores reflect one point per guideline met. DASH adherence was calculated from 24-hour dietary recalls, with one point per nine nutrient goals. Results: In 1293 women, the mean (SE) age was 36.4 (0.25) years. Black and Hispanic women with HTN were less likely than White women to have total cholesterol &lt;200 mg/dL (39% and 38% vs 47%, both p &lt;0.05), hemoglobin A1c &lt;6.5% (83% and 84% vs 92%, both p &lt;0.05), and BMI &lt;25 (13% and 16% vs 25%, p &lt;0.001 and p &lt;0.05), while Asian women had higher DASH adherence than White women (16% vs 6.5%, p &lt;0.05) (Table). The mean LS7 score was higher in Asian women (3.89 (0.09), p &lt;0.05), lower in Black women (3.16 (0.05), p &lt;0.05), and similar in Hispanic women (3.34 (0.05)) compared to White women (3.40 (0.06)). Conclusions: We found frequent comorbidities in women of childbearing age with HTN along with racial/ethnic differences in LS7 scores. Interventions to increase LS7 scores may promote health equity and reduce pregnancy-related complications.
Abstract 12428: An Unwelcome House Guest: Coronary Aneurysms and Evolving Stemi
Authors: Tara A Holder, Andrew Cluckey, Pete Fong, Jeffrey Carr, Joshua A Beckman
Journal: Circulation (2022)

Case Description: 54-year-old man presented to the Emergency Department (ED) three weeks after Covid-19 infection for progressively worsening dyspnea and hypoxemia. Dexamethasone and prophylactic apixaban (2.5mg twice a day) were initiated and he was discharged 48 hours later. A week after discharge he re-presented to the ED requiring 6L of oxygen (O 2 ) despite uninterrupted dexamethasone and apixaban therapy. His past medical history was significant for quiescent IgG4 disease on Rituximab and Type 1 Diabetes. He was afebrile, tachycardic and tachypneic with decreased right lower lobe breath sounds. He had an elevated erythrocyte sedimentation rate and C-reactive protein, no leukocytosis and no pulmonary embolism of CT. He was admitted and vancomycin and cefepime antibiotic therapy for a superimposed bacterial pneumonia was begun. On day 12 of the hospital stay, he experienced new onset chest pain. Evaluation showed an elevated troponin and submillimeter ST segment elevation concerning for an evolving STEMI. Coronary angiography demonstrated an 90% diffuse mid LAD stenosis and two large coronary aneurysms of the left circumflex artery (LCx). The mid-LAD was stented using a 3.0 x 38 mm and 2.75 x 26 mm Onyx drug eluting stents with resolution of his chest pain. IgG4 serum level was normal and imaging did not demonstrate active IgG4 disease. He was discharged on aspirin and clopidogrel. Due to concern for a hypercoagulable state in the setting of Covid 19 infection, IgG4 disease and the large coronary aneurysms for thrombus formation, warfarin anticoagulation was also initiated. On review of his coronary imaging, the largest LCx aneurysm was 9mm on admission and 12mm three weeks later with evidence of diffuse coronary inflammation. CT Fractional Flow Reserve (abnormal ≤ 0.80) demonstrated decreased flow at the distal aneurysm with no focal stenosis to account for flow reduction. Conclusion: 54-year-old man with IgG4 disease presenting with prolonged Covid-19 infection and acute NSTEMI. He was found to have large, flow limiting coronary aneurysms and inflamed coronary arteries all consistent with his IgG4 disease. Management of these aneurysms will be discussed.
Abstract 11989: PiRNA Mined From Therapeutic Cell Extracellular Vesicles, Protects Cardiac Tissue Post-Injury Through Epigenetic Silencing of Pick1 in Circulating Macrophages
Authors: Alessandra Ciullo, Liang Li, Chang Li, Eduardo Marban, Ahmed G Ibrahim
Journal: Circulation (2022)

Introduction: Small non-coding RNAs (snRNAs) comprise the majority of extracellular vesicle (EV) cargo. Therapeutic cells secrete EVs replete with snRNAs that repair damaged tissue through gene regulation in target cells. Piwi RNAs (piRNAs) are the most diverse class of snRNAs and a major component of EVs (called IMEX) secreted by engineered cardiosphere-derived cells. While much is known about the role of piRNAs in germline cells, little is known about their mechanism in tissue repair. Here we investigate the role of an enriched piRNA (piR-33044, we dub TEP3.4) in cardioprotection. Methods: W e used ischemia/reperfusion (I/R) injury in rats to evaluate the cardioprotective effect of TEP3.4. To identify a target cell type, we exposed bone-marrow-derived macrophages (BMDMs), cardiac fibroblasts, and cardiomyocytes to TEP3.4 to assess transcriptomic changes. To identify the gene target of TEP3.4, we performed whole-genome bisulfite sequencing (WGBS) and methylation-specific sequencing. Finally, to evaluate the role of macrophages in TEP3.4 cardioprotection, we adoptively transferred BMDMs exposed to TEP3.4 in I/R injury. Results: In vivo , TEP3.4 reduced infarct size (TEP3.4: 3.45±0.43g vs vehicle: 11.41±1.32g or scramble: 11.88±2.44g) and circulating cardiac troponin I (TEP3.4: 5.79±0.83ng/ml vs vehicle: 19.16±2.81ng/ml or scramble: 17.42±2.07ng/ml). BMDMs showed more transcriptomic changes compared to cardiac fibroblasts or cardiomyocytes (5435 genes vs 4114 and 2653, respectively). Methylation analysis identified pick1 as a target of TEP3.4. Pick1 downregulation enhanced Smad3 phosphorylation and phagocytic capacity in BMDMs. In vivo, Adoptive transfer of BMDMs exposed to TEP3.4 or pick1 silencing reduced infarct size (TEP3.4: 6.55± 0.85g vs vehicle: 16.73±2.13 or scramble: 16.15±3.43g in scramble) and cardiac troponin I (TEP3.4: 7.62 ±0.83ng/ml vs vehicle: 13.27 ±3.09ng/ml or scramble:15.24 ±4.04ng/ml). Conclusions: TEP3.4 exerts cardioprotection through methylation of pick1 and enhances phagocytosis in infiltrating macrophages. Pick1 downregulation in macrophages enhances phagocytosis and potentiates tissue healing and repair.
Abstract 11394: The Yield of Stress Myocardial Perfusion Imaging in Patients With Chest Pain and Low Pretest Probability of Coronary Artery Disease
Authors: Ahmed H Aljizeeri, Amjad M Ahmed, Mohammed Zayed, Mousa AlaliAlfaris, Awadelkarim Elneama, Ihab Suliman, Mohsen Alharthi, Ahmed A Alsaileek, Mouaz Al-Mallah
Journal: Circulation (2022)

Introduction: Chest pain is a common presentation in the emergency department and physician office visits. Identifying coronary artery disease (CAD) as the cause of chest pain is essential for improving prognosis. The 2021 AHA/ACC guidelines do not advocate for testing in patients with low pretest probability (PTP &lt;15%) of CAD. However, the pretest probability does not account for CAD risk factors. We sought to evaluate the yield of stress myocardial perfusion imaging (MPI) in patients with chest pain and low PTP of CAD in a population with a high prevalence of CAD risk factors. Methods: We reviewed all the patients referred to positron emission tomography from May 2011 to January 2022. Patients with chest pain and low PTP of CAD were included in the analysis. Patients with heart failure and valvular heart disease were excluded. Low PTP was defined as ≤15% on Juarez-Orozco classification. Moderate-severe ischemia is defined as ≥10% ischemic myocardium. Results: 2235 patients (age 54.2 ± 9.3 years, 23.8% males) with low PTP of CAD were included in the analysis. 303 (13.6%) of the cohort had ischemia out of which 100 (33%) patients had moderate-severe ischemia. Patients with ischemia had more prevalence of diabetes, hypertension, and hypercholesterolemia. The presence of two risk factors was associated with a higher likelihood of moderate-severe ischemia (OR = 2.2, 95%CI: 1.1 - 4.4, p=0.025) Conclusions: Ischemia is common among patients with low PTP of CAD and a high prevalence of risk factors. The presence of two risk factors is associated with a more than 2-fold increase in the risk of moderate-severe ischemia. Risk factors should be taken into consideration when deciding about further testing in this population. Further studies are needed to verify the prognostic value of testing in this population
Abstract 11279: Reporting of Diversity and Inclusion in Clinical Trials of Exercise Therapy for Peripheral Vascular Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Kavin Sundaram
Journal: Circulation (2022)

Introduction: Exercise therapy serves as a cornerstone of treatment for all patients with peripheral arterial disease (PAD); however, data suggest that women and minority groups with PAD suffer from disparate outcomes. Hypothesis: Randomized controlled trials (RCTs) of exercise therapy for PAD will demonstrate high rates of reporting and recruitment of women and minority groups. Methods: Databases were queried for RCTs that assessed the role of exercise therapy for PAD (Figure 1). Results: Only 2/47 (4%) of studies reported details of racial and ethnic subgroups (Figure 2). A meta-analysis of participation among non-white participants showed high heterogeneity (pooled effect 32%, I2 74%, p&lt;0.01, Figure 3) Meta-analysis of female recruitment and participation showed significant heterogeneity (pooled effect 26%, I2 76%, p&lt;0.01, Figure 4) with no improvement over time in meta-regression. Conclusions: Reporting and inclusion of women and minority groups remain low. Improved inclusion may help support the generalizability of the existing literature.
Abstract 11782: Senolytic Therapy Improves Diastolic Cardiac Function in Aged Mice
Authors: Eric Tuday, Torikul Islam, Johntaehwan Kim, Lisa A Lesniewski, Anthony Donato
Journal: Circulation (2022)

Introduction: Cellular senescence, an irreversible arrest of the cell cycle, is a recognized hallmark of aging that contributes to age-related multi-organ dysfunction and diseases. Evidence suggests that cardiomyocyte senescence plays a critical role in the development of age-related cardiac dysfunction. We tested the hypothesis that targeting senescent cells via intermittent administration of the senolytic drugs dasatinib and quercetin (D&amp;Q) will improve cardiac dysfunction in old mice. Methods: 21-month-old C57Bl/6 mice were treated with D&amp;Q or vehicle via oral gavage on a bi-monthly basis for three months. Systolic and diastolic cardiac function were assessed using echocardiography. Expression of inflammatory and matrix metalloproteinase genes was assessed using quantitative polymerase chain reactions. Cardiac tissue morphology was assessed by histological analysis. Results: D&amp;Q treatment improved ejection fraction (EF) in old mice (60.3% vs. 64.5%, con vs. D&amp;Q, p = 0.0207, n=18). Global longitudinal strain was improved by D&amp;Q treatment (-13.99% vs. -17.03%, con vs. D&amp;Q, p=.0005, n=18). Measures of diastolic function were improved after D&amp;Q treatment (n=18 for all): E/E’ (27.60 vs. 20.08, con vs. D&amp;Q, p&lt;.0001), isovolumetric relaxation time (IVRT, 22.74ms vs. 14.99ms, con vs. D&amp;Q, p&lt;.0001), and reverse longitudinal strain rate (rLSR, 4.64 1/s vs. 13.41 1/s, con vs. D&amp;Q, p&lt;.0001). Expression of inflammatory and matrix metalloproteinase genes ( cd3e, foxp3, tnf- α, mcp-1, mmp9 ) was lower in hearts from D&amp;Q treated compared to control mice (p≤0.05). Extracellular matrix collagen expression was lower in cardiac tissue from D&amp;Q treated compared to control (p&lt;0.01). Conclusions: For the first time we report a significant improvement in diastolic function in aged mice when treated long term with the senolytic therapy dasatinib and quercetin. Measurements of systolic function also improved, but not to the same degree as observed for diastolic function. Overall, senolytic therapy with D&amp;Q represents an attractive option to explore for the treatment of diastolic heart failure in humans.